EXCHANGE 


LIPHATIC  ARSONIC  AND  ARSINIC  ACIDS  AND 
ALIPHATIC-AROMATIC  ARSINIC  ACIDS 


By 

ARMAND  JAMES  QUICK 

B.  S.  University  of  Wisconsin,  1918 
M.  S.  University  of  Wisconsin,  1919 


THESIS 

SUBMITTED   IN  PARTIAL  FULFILLMENT  OF   THE   REQUIREMENTS 

FOR  THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY  IN  CHEMISTRY 

IN  THE  GRADUATE  SCHOOL  OF  THE  UNIVERSITY 

OF  ILLINOIS,  1922 


. 


URBANA,  ILLINOIS 


Reprinted  from  the  JOUENAL  OF  THE  AMERICAN  CHEMICAL  SOCIETY, 
Vol.  XLIV.     No.  4.    April,  1922. 


ALIPHATIC  ARSONIC  AND  ARSINIC  ACIDS  AND 
ALIPHATIC-AROMATIC  ARSINIC  ACIDS 


By 

ARMAND  JAMES  QUICK 

B.  S.  University  of  Wisconsin,  1918 
M.  S.  University  of  Wisconsin,  1919 


THESIS 

SUBMITTED    IN    PARTIAL   FULFILLMENT    OF    THE    REQUIREMENTS 

FOR  THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY  IN  CHEMISTRY 

IN  THE  GRADUATE  SCHOOL  OF  THE  UNIVERSITY 

OF  ILLINOIS,  1922 


URBANA,  ILLINOIS 


Reprinted  from  the  JOURNAL  OF  THE  AMERICAN  CHEMICAL  SOCIETY, 
Vol.  XLIV.     No.   4.     April,  1922. 


78642 


ACKNOWLEDGMENT 

This  investigation  was  undertaken  at  the  suggestion  of 
Professor  Roger  Adams  and  was  carried  out  under  his  direct- 
ions. The  author  wishes  to  express  his  gratitude  to  him  for 
his  generous  assistance  and  advice  throughout  this  work. 


[Reprinted  from  the  Journal  of  the  American  Chemical  Society, 
Vol.  XLIV.     No.  4.     April,  1922.] 


[CONTRIBUTION  PROM  THE  CHEMICAL  LABORATORY  OF  THE  UNIVERSITY  OF  ILLINOIS] 

ALIPHATIC  ARSONIC  AND  ARSINIC  ACIDS,  AND  ALIPHATIC- 
AROMATIC  ARSINIC  ACIDS1 

BY  A.  J.  QUICK  WITH  ROGER  ADAMS 

Received  December  26,  1921 

The  extensive  development  of  aromatic  arsenicals  as  compared  with  those 
of  the  aliphatic  series  is  in  part  explained  by  the  fact  that  the  most  active 
and  most  effective  trypanocidal  drugs  belong  to  the  aromatic  series. 
Another  cause  for  the  unbalanced  development  is  found  in  the  ease  and 
convenience  with  which  aromatic  arsenicals  can  be  synthesized.  The 
methods  of  preparation  for  the  arsenic  compounds  belonging  to  the  ali- 
phatic series  are  very  numerous,2  but  they  are  quite  unsatisfactory. 

The  arsonic  (RAsO3H2)  and,  to  a  less  extent,  the  arsinic  acids  (R2AsO2H) 
are  substances  from  which  many  different  types  of  compounds  may  be 
made,  so  that  the  lack  of  a  satisfactory  method  of  preparation  of  these  has 
limited  development  in  this  field.  The  object  of  this  research  was  to  find 
an  easy  method  for  preparing  these  compounds  and  to  apply  such  a  method 

1  This  communication  is  an  abstract  of  a  thesis  submitted  by  A.  J.  Quick  in  partial 
fulfilment  of  the  requirements  for  the  degree  of  Doctor  of  Philosophy  in  Chemistry  at 
the  University  of  Illinois. 

2  See  THIS  JOURNAL,  28,  347  (1906)  for  a  list  of  the  known  methods. 


806 


:: ."-':  i-:j*ieuie^VwiTH  ROGER  ADAMS 


to  the  preparation  of  certain  aliphatic-aromatic  acids  which  might  have 
therapeutic  value. 

Of  all  methods  available  for  preparing  primary  and  secondary  arsenic 
compounds,  only  one,  namely  the  Meyer  reaction,  has  any  great  importance. 
This  consists  in  the  treatment  of  sodium  arsenite  with  an  alkyl  halide  to 
give  an  arsonic  acid,  or  the  treatment  of  a  sodium  alkyl  arsenite  with  an 
alkyl  halide  to  give  an  arsinic  acid.3 

The  reaction  was  first  studied  by  G.  Meyer4  in  1883.  Klinger  and 
Kreutz8  reinvestigated  the  reaction  and  developed  it  into  a  practical  method 
for  the  preparation  of  sodium  methyl  arsonate.  Auger6  showed  its  appli- 
cation to  the  formation  of  dimethyl  arsinic  acid.  Dehn7  applied  the 
method  to  the  general  synthesis  of  arsonic  acids  and  obtained  the  salts  of 
a  number,  of  the  higher  homologs  in  this  way.  It  was  necessary  to  use  a 
rather  uncertain  and  tedious  procedure,  however,  for  getting  rid  of  the 
impurities  and  for  the  isolation  of  the  product.  Valeur  and  Delaby8 
reinvestigated  the  action  of  ethyl  iodide  on  potassium  arsenite,  but  added 
little  to  what  was  previously  known  so  far  as  the  isolation  of  the  product 
was  concerned. 

The  possibilities  of  the  Meyer  reaction  were  recognized  to  some  extent 
in  the  preparation  of  toxic  gases  during  the  recent  war.  Ethyl  dichloro- 
arsine,  which  was  used  by  Germany,  was  prepared  by  the  action  of  ethyl 
chloride  on  sodium  arsenite  under  pressure,9  then  subsequent  reduction 
and  treatment  with  hydrochloric  acid.  In  this  country  methyl  dichloro- 
arsine  was  prepared  by  the  action  of  dimethyl  sulfate  on  sodium  arsenite,10 
then  subsequent  reduction  and  treatment  with  hydrochloric  acid.  More 
recently  methyl  di-iodo-arsine11  has  been  made  in  an  analogous  manner 
except  that  methyl  iodide  was  used  in  place  of  dimethyl  sulfate.  In  none 
of  these  cases,  however,  was  the  arsonic  acid  isolated. 

The  greatest  disadvantage  at  present  in  the  Meyer  method  for  making 
arsonic  acids  lies  in  the  difficulty  with  which  the  products  are  isolated. 
The  method,  as  it  has  been  used,  consists  in  the  treatment  of  an  aqueous 
alcoholic  solution  of  sodium  arsenite  with  an  alkyl  iodide  until  titration 
3  It  is  probable  that  the  alkyl  halide  reacts  with  the.  tautomeric  forms  of  the  sodium 
arsenite  or  sodium  alkyl  arsonite  in  each  instance  (Na2O3AsNa  and  RNaC^AsNa) 
thus  producing  compounds  with  the  alkyl  radical  attached  to  arsenic. 

Na3AsO3  +  RI  >  RAsOaNa,  +  Nal 

RAsO2Na2  +  RI  — >  R2AsO2Na  +  Nal 
«  Meyer,  Ber.,  16,  1440  (1883). 
6  Klinger  and  Kreutz,  Ann.,  249,  147  (1903). 

6  Auger,  Compt.  rend.,  137,  925  (1903). 

7  Dehn,  Am.  Chem.  J.,  35,  48  (1906);  THIS  JOURNAL,  28,  357  (1906). 
s  Valeur  and  Delaby,  Bull.  soc.  chim.,  27,  370  (1920). 

9  /.  Jnd.  Eng.  Chem.,  11,  817  (1919). 

10  Ibid.,  11,  105  (1919). 

11  /.  Chem.  Soc.,  119,  426  (1921). 


ALIPHATIC  ARSONIC  AND  ARSINIC  ACIDS  807 

shows  that  most  of  the  arsenite  has  reacted.  When  methyl  iodide  has 
been  used  the  reaction  mixture  is  merely  allowed  to  cool  and  the  sodium 
methylarsonate  being  insoluble  in  dilute  alcohol,  precipitates  in  practically 
pure  state.  The  isolation  of  the  higher  homologs,  however,  is  not  so  simple 
since  the  sodium  salts  are  soluble  in  the  dilute  alcohol.  In  these  latter 
cases,  the  method  that  has  been  employed  is  to  distil  the  alcohol  and  any 
ether  that  is  formed  in  the  reaction,  to  acidify  to  incipient  precipitation, 
then  to  oxidize  the  excess  of  sodium  arsenite  to  sodium  arsenate  by  means 
of  chlorine  and  at  the  same  time  to  precipitate  free  iodine,  to  filter  the 
iodine,  to  precipitate  the  sodium  arsenate  in  the  cold  with  magnesia 
mixture,  to  filter  this  and  finally  precipitate  the  magnesium  salt  of  the  ar- 
sonic  acid  by  boiling  with  an  excess  of  magnesia  mixture.  The  difficulties 
that  must  arise  in  obtaining  a  product  in  this  way,  especially  one  that  is 
pure,  can  readily  be  seen.  Moreover,  Valeur  and  Delaby  found  that  in 
the  presence  of  aqueous  alcoholic  sodium  arsenite,  over  50%  of  the  ethyl 
iodide  is  converted  to  ether,  thus  necessitating  a  large  excess  of  the  alkyl 
halide.  The  ether  formation  undoubtedly  occurs  in  the  preparation  of 
ar sonic  acids  of  higher  molecular  weight. 

In  order  to  make  the  Meyer  reaction  applicable  for  wider  synthetic 
work  the  objectionable  features  pointed  out  were  eliminated.  Alkyl 
bromides  or  chlorides  were  used  instead  of  the  iodides  so  that  the  free 
arsonic  acids  might  be  isolated  directly  by  acidification ;  this  is  not  possible 
when  an  iodide  is  used,  since  the  liberated  hydriodic  acid  formed  im- 
mediately reduces  the  arsonic  acid.  The  use  of  dilute  alcohol  as  a  solvent 
was  given  up  and  water  alone  was  used,  thus  eliminating  to  a  great  extent 
the  formation  of  ether.  Heating  and  stirring  were  employed  to  hasten 
the  reaction.  The  speed  of  the  reaction  was  determined  by  titrating  from 
time  to  time  1  or  2  cc.  of  the  reaction  mixture  with  standard  iodine  in  order 
to  show  the  amount  of  sodium  arsenite  unchanged.  The  isolation  of  the 
arsonic  acid  is  then  simple  since  it  is  merely  necessary  to  concentrate  the 
solution,  filter  off  the  sodium  halide  and  acidify.  The  arsonic  acid  is 
precipitated  in  such  form  that,  after  one  crystallization  from  alcohol  or 
water,  it  is  perfectly  pure.  With  the  higher,  less  soluble  homologs  the 
method  is  even  simpler  in  that  the  arsonic  acid  may  be  precipitated  directly 
without  concentration  from  the  reaction  mixture,  by  means  of  hydro- 
chloric acid. 

There  is  no  general  method  for  the  preparation  of  aliphatic  arsinic  acids. 
Sodium  dimethyl  arsinate  is  made  commercially  by  the  Cadet  cacodyl 
reaction,  but  this  reaction  is  limited  to  this  substance  and  at  best  is  beset 
with  experimental  difficulties.  The  condensation  of  an  alkyl  halide  with 
arsenious  chloride  by  means  of  sodium  to  produce  dialkyl  chloro-arsines 
which  can  be  converted  to  the  corresponding  arsinic  acids  by  bromination 
or  chlorination  and  then  hydrolysis,  has  been  used  as  often  as  any  other  re- 


808  A.  J.  QUICK  WITH  ROGER  ADAMS 

action  for  making  aliphatic  arsinic  acids.  The  method  is  unsatisfactory, 
however,  owing  to  the  fact  that  the  pure  dialkyl  chloro-arsines  are  difficult 
to  obtain  and  the  conversion  to  arsonic  acid  does  not  give  large  yields. 
The  Meyer  reaction  gives  very  good  results.  The  arsonic  acid  made  by  the 
Meyer  method  is  readily  reduced  with  sulfur  dioxide  in  the  presence  of 
hydrochloric  acid  to  give  good  yields  of  the  alkyl  dichloro-arsine.  This 
latter  product  is  separated,  then  dissolved  in  4  moles  of  sodium  hydroxide 
and  treated  with  an  alkyl  halide  under  the  same  conditions  used  in  the 
preparation  of  arsonic  acids.  The  reactions  take  place  rapidly,  only  4 
hours  or  less  being  required  in  order  to  prepare  any  of  the  arsinic  acids 
studied.  The  isolation  of  some  of  the  arsinic  acids,  however,  is  a  little 
more  difficult  than  the  isolation  of  the  arsonic  acids,  on  account  of  the  great 
solubility  in  water  of  the  lower  homologs.  It  is  necessary  to  neutralize  the 
solution,  then  to  concentrate  and  filter  out  the  inorganic  salts,  and  finally 
to  acidify  in  order  to  precipitate  the  arsinic  acid.  If  a  salt  of  the  arsinic 
acid  is  desired,  the  copper  dialkyl  arsinates  are  readily  precipitated  from  a 
neutral  solution  by  means  of  copper  sulfate. 

In  studying  the  action  of  various  alkyl  bromides  or  chlorides  on  sodium 
arsenite  or  sodium  alkyl  arsenites,  the  activity  of  the  halogen  in  the  alkyl 
halide  and  the  solubility  of  the  alkyl  halide  are  very  important  factors  in 
determining  the  speed  of  reaction.  Benzyl  chloride,  allyl  bromide  and  ethyl- 
ene  chlorohydrin  react  very  rapidly, whereas  ethyl  bromide  or  more  partic- 
ularly isopropyl  bromide  react  slowly.  The  three  halides  just  mentioned 
which  react  rapidly,  give  practically  a  complete  conversion  in  Ve  to  Vio  the 
time  necessary  with  the  simple  alkyl  halides.  It  is  noticeable  that  with  a 
series  of  alkyl  halides  the  speed  of  reaction  diminishes  as  the  molecular 
weight  of  the  alkyl  halide  is  increased.  Aryl  halides  cannot  be  used  in  this 
reaction.  It  was  found  also  that  phenoxy  alkyl  bromides  or  ethylene  dibrom- 
ide  do  not  react  with  sodium  arsenite  under  the  conditions  used. 

The  investigation  on  the  arsinic  and  arsonic  acids  which  has  just  been 
described  was  undertaken  in  connection  with  other  researches,  carried  out 
with  funds  furnished  by  the  Interdepartmental  Social  Hygiene  Board, 
which  had  as  their  object  the  discovery  of  arsenic  'compounds  of  low 
toxicity  and  high  trypanocidal  action.  All  such  active  substances  which 
have  so  far  been  discovered  contain  nitrogen.  Moreover,  this  nitrogen  has 
been  in  the  form  of  an  amino  or  substituted  amino  group  in  a  benzene  ring 
which  holds  the  arsenic  either  in  the  form  of  an  arsonic  acid  group  or  arseno 
group.  A  number  of  new  arsenic  compounds  belonging  to  the  class  of 
aromatic-aliphatic  arsinic  acids  have  been  prepared  in  some  of  which  the 
nitrogen  is  substituted  in  the  aliphatic  group  which  is  attached  to  the  ar- 
senic, and  in  others  of  which  the  nitrogen  is  both  in  the  benzene  ring  holding 
the  arsenic  as  well  as  in  the  aliphatic  group.  These  substances  may  be 
represented  by  the  compound  formed  between  sodium  phenyl  arsenite  and 
chloro-acetanilide . 


ALIPHATIC  ARSONIC  AND  ARSINIC  ACIDS 

C1CH2CONHR  — >  C6H5As(O2Na)CH2CONHR  +  NaCl. 
Compounds  of  this  general  structure  are  extremely  easily  produced  by 
using  practically  the  same  conditions  which  are  described  for  the  prepara- 
tion of  the  dialkyl  arsinic  acids.  Because  of  the  slight  solubility  in  water 
of  the  reaction  products,  they  are  very  readily  isolated  as  the  free  acids. 
The  reactions  in  practically  every  instance  take  place  within  a  very  few 
hours,  and  the  yields  are  very  nearly  quantitative.  The  preliminary 
pharmacological  results12  show  that  these  substances  have  a  low  toxicity, 
the  lethal  dose  for  rabbits  varying  from  250  to  over  600  mg.  per  kg.  of 
body  weight.  At  the  same  time,  however,  the  trypanocidal  action  is  nil  in 
some  of  the  compounds,  or  low  in  most  of  the  compounds,  even  though 
administered  in  relatively  large  amounts. 

The  reactions  between  sodium  phenyl  arsenite  and  various  halogen 
compounds  run  just  as  smoothly  as  the  sodium  alkyl  arsenites  and  much 
more  readily  than  with  the  sodium  arsenite.  Whereas  the  phenoxyalkyl 
halides  or  ethylene  dibromide  do  not  react  with  sodium  arsenite,  they  do 
react  with  the  sodium  alkyl  or  aryl  arsenites  to  give  the  expected  con- 
densation products.  The  simple  alkyl  halides  peculiarly,  when  condensed 
with  sodium  phenyl  arsenite,  give  oily  reaction  products,  although  these 
substances  when  pure  are  crystalline  solids.13  A  number  of  other  con- 
densations that  were  attempted  yielded  oily  products  and  a  method  has  not 
yet  been  developed  by  which  these  oils  may  be  obtained  as  crystalline 
solids. 

Experimental 
Synthesis  of  Arsonic  Acids 

General  Procedure.14 — One  mole  of  arsenious  oxide  is  dissolved  in 
sufficient  10  N  sodium  hydroxide  solution  to  produce  tri-sodium  arsenite. 
This  is  placed  in  a  round-bottom  flask  fitted  with  an  efficient  mechanical 
stirrer  and  a  reflux  condenser.  Slightly  more  than  a  mole  of  alkyl  halide 
is  added  and  the  mixture  stirred  and  refluxed  until  a  cubic  centitneter 
withdrawn  from  the  reaction  mixture  and  titrated  with  standard  iodine 
shows  that  most  of  the  sodium  arsenite  (80  to  90%)  has  reacted.  The 
method  of  isolation  is  slightly  different  in  each  case  and  will  be  described 
under  the  individual  compounds.  In  every  case  acidification  with  hydro- 
chloric acid  is  involved.  Excess  acid  must  be  avoided,  as  it  tends  to  dis- 
solve the  arsonic  acids. 

Sodium  Methyl  Arsonate,15  CHsAsOa^.— The  reaction  between  99  g.  of  arsenious 
oxide,  300  cc.  of  10  N  sodium  hydroxide  solution  and  150  g.  of  methyl  iodide  on  warming 

12  Detailed  pharmacological  results  will  be  published  by  Dr.  A.  S.  Loevenhart  of  the 
University  of  Wisconsin  when  the  investigation  is  completed. 

»  Ber.,  48,  350  (1915). 

14  All  analyses  for  arsenic  were  done  by  the  method  described  by  Robertson,  THIS 
JOURNAL,  43, 182  (1921). 

»  Ann.,  249,  147  (1903). 


810  A.  J.  QUICK  WITH  ROGER  ADAMS 

is  complete  in  about  2  hours.  An  equal  volume  of  alcohol  is  added  to  the  mixture 
and  the  sodium  methyl  arsonate  precipitates  in  very  good  yields.  The  product  may  be 
purified  by  dissolving  in  a  small  amount  of  water  and  reprecipitating  with  alcohol. 

Ethyl  Arsonic  Acid,  CzHsAsOsHz. — The  reaction  between  198  g.  of  arsenious 
oxide,  300  cc.  of  10  N  sodium  hydroxide  solution  and  175  g.  of  ethyl  bromide  (110  g.  is 
added  at  the  beginning  and  50  to  65  g.  added  gradually  during  the  course  of  the  reaction 
to  compensate  any  loss  due  to  volatilization),  requires  24  to  48  hours  before  it  is  90%  com- 
plete. The  reaction  mixture  is  concentrated  to  a  little  less  than  half  of  its  original 
volume  and  filtered  to  remove  the  sodium  bromide  which  separates.  The  filtrate 
is  now  made  neutral  to  phenol phthalein  with  hydrochloric  acid,  again  concentrated  to 
*/2  or  2/3  its  volume  and  filtered  from  sodium  halide.  It  is  next  acidified  with  hydro- 
chloric acid  till  congo  red  just  commences  to  turn  blue,  once  more  concentrated  to 
l/z  or  2/3  its  volume  and  filtered  from  sodium  halide  while  still  hot.  On  cooling,  about 
80  g.  of  needle-like  crystals  separates,  together  with  a  small  quantity  of  sodium  chloride. 
The  filtrate  will  yield  a  larger  quantity  of  ethyl  arsonic  acid  if  it  is  concentrated,  filtered 
hot  from  the  sodium  halide  and  allowed  to  cool.  This  last  treatment  is  repeated 
and  from  these  two  concentrations  about  40  g.  more  of  arsonic  acid  is  obtained.  The 
total  yield  of  120  g.  is  best  purified  from  traces  of  salts  by  crystallizing  from  a  small 
amount  of  water.  The  product  then  melts  at  95-96°  which  is  the  same  melting  point 
as  was  found  by  La  Coste.16 

w-Propyl  Arsonic  Acid,  C3H7AsO3H2. — The  reaction  bebween  99  g.  of  arsenious 
oxide,  300  cc.  of  10  N  sodium  hydroxide  solution  and  123  g.  of  w-propyl  bromide  requires 
24  to  48  hours  for  90%  completion.  The  reaction  mixture  is  treated  exactly  as  with  the 
ethyl  arsonic  acid.  The  propyl  arsonic  acid  separates  as  small  plates.  As  the  acid  is 
less  soluble  than  the  ethyl  compound,  it  is  obtained  more  readily  and  in  better  yields. 
The  product  is  easily  purified  by  recrystallization  from  a  small  amount  of  water  and  then 
has  a  melting  point  of  126-7°  which  agrees  with  that  recorded  in  the  literature.17 

w-Butyl  Arsonic  Acid,  C-iHgAsOaHg.—  The  reaction  between  275  g.  of  w-butyl 
bromide,  198  g.  of  arsenious  oxide  and  600  cc.  of  10  N  sodium  hydroxide  solution  re- 
quires 40  to  60  hours  before  90%  of  the  arsenious  oxide  has  reacted.  Small  amounts  of 
butyl  bromide  and  butyl  alcohol  which  have  formed  by  hydrolysis  are  distilled  and  the 
solution  is  then  neutralized  to  phenolphthalein  with  hydrochloric  acid,  concentrated  to 
about  half  its  volume  and  filtered.  Upon  adding  hydrochloric  acid  till  congo  red  just 
commences  to  turn  blue,  butyl  arsonic  acid  separates  as  a  thick  crystalline  paste.  About 
300  g.  of  the  crude  material  is  thus  obtained.  It  is  readily  purified  by  a  crystallization 
or  two  from  hot  water.  It  may  also  be  recrystallized  from  alcohol.  Butyl  arsonic  acid 
melts  at  159-160°  and  in  its  general  properties  resembles  the  other  arsonic  acids.  It 
forms  an  insoluble  magnesium  salt  with  magnesia  mixture. 

Analyses.  Subs.,  0.2000,  0.2000:  required  21.2.  21.2  cc.  of  0.1038  N  I.  Calc.  for 
C4HnO3As:  As,  41.2.  Found:  41.2,  41.2. 

Allyl  Arsonic  Acid,  CB2  =  CHCH2AsO3H8.18— The  reaction  between  250  g.  of  allyl 
bromide,  198  g.  of  arsenious  oxide  and  600  cc.  of  10  N  sodium  hydroxide  solution  is 
90%  complete  in  2  to  3  hours.  The  reaction  mixture  is  neutralized  to  phenolphthalein 
with  hydrochloric  acid,  concentrated  to  about  1A  of  its  original  volume  and  filtered. 
On  acidifying  the  filtrate  till  congo  red  just  commences  to  turn  blue,  the  allyl  arsonic 

16  La  Coste,  Ann.,  208, 34  (1881). 

17  THIS  JOURNAL,,  28,  352  (1906). 

18  During  the  preparation  of  this  communication,  an  abstract  of  an  English  patent 
has  appeared  which  describes  the  production  of  allyl  arsonic  acid  and  its  salts.     The 
procedure  is  somewhat  different  from  the  one  used  in  this  investigation.     Brit.   pat. 
167,157;  Zentr.,  1921,  II,  1065. 


ARSONIC  AND  ARSINIC  ACIDS  8ll 

acid  precipitates  in  needle-like  crystals,  with  a  small  amount  of  sodium  chloride.  The 
mixture  is  heated  to  boiling  and  filtered  hot,  thus  removing  most  of  the  salt.  The 
filtrate  deposits  crystals  on  cooling.  These  weigh  270  g.,  are  pure  after  one  recrystal- 
lization  from  water,  and  then  melt  at  128-9  °. 

Analysis.  Subs.,  0.2000:  reauired  26.4  cc.  of  0.09205  N  I.  Calc.  for  C3H7O3As: 
As,  45.2.  Found:  45.4. 

Benzyl  Arsenic  Acid,19  CeHsCJ^AsOsH^.  —  The  reaction  between  126  g.  of  benzyl 
chloride,  99  g.  of  arsenious  oxide  and  300  cc.  of  10  N  sodium  hydroxide  solution  is  more 
than  90%  complete  within  2  hours.  An  oily  layer  consisting  of  benzyl  alcohol  and  a 
slight  excess  of  benzyl  chloride  is  always  present  at  the  end  of  the  reaction.  This  is 
removed  and  the  solution  carefully  neutralized  to  litmus  with  hydrochloric  acid,  then 
just  a  little  more  is  added.  On  standing  for  about  an  hour,  a  small  amount  of  flocculent 
material  separates.  This  is  filtered  and  the  filtrate  acidified  till  congo  red  commences 
to  turn  blue.  Benzyl  arsonic  acid  separates  and  is  immediately  filtered.  It  is 
washed  with  water  and  dried  at  90°.  The  yields  vary  from  about  130  to  135  g.  After 
a  crystallization  from  alcohol  or  water  it  melts  at  167-8°. 

Attempts  to  Prepare  Other  Arsonic  Acids. — Ethylene  chlorohydrin  reacts  very 
rapidly  with  sodium  arsenite  and  in  10  minutes  over  80%  of  the  arsenious  oxide  has 
disappeared.  The  product,  however,  does  not  precipitate  when  treated  in  the  way 
described  for  the  alkyl  arsonic  acids.  The  solution  is  evaporated  to  an  extremely 
small  volume,  the  sodium  halide  filtered  from  time  to  time,  and  the  residue  is  treated 
with  absolute  alcohol;  practically  all  of  the  sodium  halide  separates  and  is  filtered  off. 
Upon  evaporation  of  the  filtrate  an  oil  is  obtained  which  is  presumably  the  desired 
product,  but  as  no  method  of  purification  was  found  it  was  not  analyzed. 

Similar  results  are  obtained  with  trimethylene  bromide,  using  two  moles  of  sodium 
arsenite.  The  reaction  takes  place  slowly.  The  product  in  this  case  is  a  thick  oil  which 
does  not  solidify. 

Phenoxy-propyl  bromide,  phenoxy-ethyl  bromide,  rsopropyl  bromide  and  ethylene 
bromide  react  only  very  slowly  with  sodium  arsenite  and  no  products  were  isolated. 

General  Procedure  for  Aliphatic  Arsinic  Acids. — The  conditions  for 
the  preparation  of  the  arsinic  acids  are  almost  the  same  as  those  required 
for  the  preparation  of  arsonic  acids.  One  mole  of  alkyl  dichloro-arsine 
is  dissolved  in  sufficient  10  N  sodium  hydroxide  solution  to  produce  the 
disodium  alkyl  arsenite.  This  is  placed  in  a  round-bottom  flask  fitted 
with  an  efficient  mechanical  stirrer  and  reflux  condenser.  Slightly  more 
than  a  mole  of  alkyl  halide  is  added  and  the  mixture  stirred  and  refluxed  till 
titration  shows  that  more  than  90%  of  the  disodium  alkyl  arsenite  has 
reacted.  Wherever  the  final  products  are  only  slightly  soluble  in  water, 
direct  acidification  of  the  reaction  mixture  till  congo  red  just  commences 
to  turn  blue  will  cause  the  product  to  separate;  where  they  are  very  soluble 
in  water,  it  is  necessary  to  proceed  in  a  manner  somewhat  similar  to  that 
used  for  the  isolation  of  the  alkyl  arsonic  acids.  Excess  of  acid  causes  the 
arsinic  acids  to  become  oily,  so  must  be  avoided. 

Diethyl  Arsinic  Acid,20  (C2H6)2AsO2H.— The  reaction  between  55  g.  of  ethyl  bromide, 
90  g.  of  ethyl  dichloro-arsine  and  210  cc.  of  10  N  sodium  hydroxide  requires  from  4  to  6 
hours  before  it  is  90%  complete.  It  is  desirable  to  add  20  g.  more  of  ethyl  bromide 

19  THIS  JOURNAL,  28,  347  (1906). 

20  J.  prakt.  Chem.,  63,  283  (1854). 


812  A.  J.  QUICK  WITH  ROGER  ADAMS 

toward  the  end  of  the  reaction  in  order  to  replace  that  lost  by  volatilization.  The 
excess  of  ethyl  bromide  is  boiled  away,  the  solution  neutralized  to  phenolphthalein  with 
hydrochloric  acid,  concentrated  to  half  its  volume  and  filtered  from  the  salt  which  sepa- 
rates. The  filtrate  is  acidified  with  hydrochloric  acid  till  congo  red  just  commences  to 
turn  blue,  and  concentrated  once  more  to  about  2/s  of  its  original  volume  when 
50  g.  of  crude  diethyl  arsinic  acid  separate  in  plates.  After  two  crystallizations  from 
alcohol,  the  product  is  entirely  free  from  a  small  amount  of  sodium  chloride. 

w-Butyl  Dichloro-arsine,  C^AsCla  — A  solution  of  150  g.  of  crude  w-butyi  arsonic 
acid  in  300  cc.  of  cone,  hydrochloric  acid  is  prepared.  A  few  crystals  of  potas- 
sium iodide  are  added  as  a  catalyst  and  then  the  solution  is  saturated  with  sulfur  dioxide 
(about  2  hours  is  required).  By  this  procedure,  100  g.  of  crude  butyl  dichloro-arsine 
separates.  It  is  removed  and  the  aqueous  liquors  are  saturated  with  salt,  thus  yielding  an 
additional  quantity  of  the  dichloride.  The  product  is  fractionated  under  diminished 
pressure  and  when  pure  consists  of  a  colorless  oil  boiling  at  192-4°. 

Analysis.  Subs., 0.5035:  AgNO3, 0.8426.  Calc.for C^ClzAs:  Cl,34.9.  Found: 
34.9. 

w-Propyl  w-Butyl  Arsinic  Acid,  CJ-IoCCaHyJAsC^H.— The  reaction  between  25  g.  of 
«-butyl  dichloro-arsine,  60  cc.  of  10  N  sodium  hydroxide  solution  and  20  g.  of  «-propyl 
bromide  requires  3  to  5  hours  for  completion.  The  reaction  mixture  is  made  neutral  to 
phenolphthalein  with  hydrochloric  acid  and  then  concentrated  to  half  its  volume.  The 
salt  which  separates  is  filtered  and  the  filtrate  carefully  acidified.  The  crystalline  pre- 
cipitate of  arsinic  acid  is  filtered  and  dried,  and  weighs  16  g.  The  filtrate  is  further 
concentrated  to  about  2/s  of  its  volume,  filtered  hot  to  remove  the  salt  which  separates, 
and  then  cooled  to  obtain  a  further  amount  of  arsinic  acid.  The  crude  product  must  be 
crystallized  once  or  twice  from  water  to  free  it  from  sodium  chloride,  and  then  melts 
at  127-8°. 

Analyses.  Subs.,  0.2000,  0.2000:  required  21.1,  21.0  cc.  of  0.09205  N  I.  Calc.for 
C7H17O2As:  As,  36.0.  Found:  36.2,36.1. 

Di-w-butyl  Arsinic  Acid,  (CJIg^AsC^H.— The  reaction  between  61  g.  of  w-butyl 
bromide,  90  g.  of  butyl  dichloro-arsine  and  180  cc.  of  10  N  sodium  hydroxide  solution 
requires  3  hours  for  completion.  The  solution  is  neutralized,  concentrated,  and  the  salt 
filtered  as  described  in  the  previous  experiments.  The  filtrate  is  carefully  acidified  till 
congo  red  just  commences  to  turn  blue,  and  the  crystalline  dibutyl  arsinic  acid  separates. 
After  washing  and  drying  it  weighs  85  g.  and  after  one  crystallization  from  water  it  is 
perfectly  pure  and  melts  at  137-8°.  Considerable  care  should  be  taken  in  acidifying 
the  solution  in  order  to  precipitate  the  arsinic  acid,  since  excess  of  acid  causes  the  product 
to  become  oily. 

Analysis,  Subs.,  0.2000:  required  19.65  cc.  of  0.09205  N  I.  Calc.  for  C8Hi0O2As: 
As,  33.8.  Found:  33.8. 

The  light-blue  COPPER  SALT,  [(C4H9)AsO2]2Cu,  is  readily  precipitated  from  a  solu- 
tion of  dibutyl  arsinic  acid  which  has  been  just  neutralized  to  phenolphthalein  with 
sodium  hydroxide  by  adding  copper  sulfate  solution.  The  product  is  filtered,  washed 
and  dried  for  2  hours  at  90°  in  a  vacuum.  The  yield  is  nearly  quantitative. 

Analysis.  Subs.,  0.2000:  required  17.0  cc.  of  0.09205  NI.  Calc.  for  CgHigC^stCu: 
As,  29.6.  Found:  29.2. 

General  Procedure  for  Aliphatic-aromatic  Arsinic  Acids. — One  mole  of 
the  dichloro-arsine  is  dissolved  in  4  moles  of  alkali  in  the  usual  way  and  1 
mole  of  the  halogen  compound  added  gradually,  generally  at  room 
temperature.  The  reactions  take  place  rapidly  enough  so  that  with  the 


ALIPHATIC  ARSONIC  AND  ARSINIC  ACIDS  813 

sodium  aromatic  arsenites  neither  heating  nor  stirring  are  necessary  in  most 
cases  to  give  excellent  results.  To  isolate  the  products  which  for  the  most 
part  are  not  very  soluble  in  water,  the  reaction  mixture  is  made  neutral  to 
phenolphthalein  with  hydrochloric  acid.  This  causes  the  precipitation  of  a 
small  amount  of  unchanged  aromatic  arsine  oxide  which  is  filtered.  The 
filtrate  is  made  acid  with  hydrochloric  acid  until  congo  red  just  com- 
mences to  turn  blue,  to  precipitate  the  product.  If  the  product  contains 
an  amino  group  the  final  acidification  must  be  done  with  care,  not  enough 
acid  being  added  to  redissolve  the  precipitate. 

The  majority  of  these  compounds  have  decomposition  points  and  not 
melting  points.  It  was  found  that  the  decomposition  points  may 
vary  considerably  with  the  speed  at  which  the  temperature  of  the  bath  is 
raised. 

Phenylarsino  Acetic  Acid,  C6H5As(O2H)CH2CO2H.— A  mixture  of  180  g.  of 
phenyl  dichloro-arsine  and  365  cc.  of  10  N  sodium  hydroxide  solution  is  cooled  and  to 
this  solution  is  added  gradually  with  stirring  121  g.  of  sodium  chloro-acetate  in  150  cc. 
of  water.  An  immediate  reaction  takes  place  and  is  complete  within  about  30  minutes, 
but  it  is  best  to  allow  the  mixture  to  stand  for  2  to  3  hours  longer.  The  yield  of  product 
is  120  g.  The  substance  may  be  purified  by  crystallization  from  hot  water  and  then 
melts  at  141-2°  with  decomposition. 

Analysis.  Subs.,  0.2000:  required  17.8  cc.  of  0.09205  N  I.  Calc.  for  C8H9O<As: 
As,  30.7.  Found:  30.6. 

Phenyl  Chloro-arsine  Acetic  Acid,  CeH^AsClCH-sCOszH.— A  solution  is  made  of  60  g. 
of  phenylarsino  acetic  acid  in  180  cc.  of  cone,  hydrochloric  acid  to  which  a  few 
crystals  of  potassium  iodide  have  been  added.  Sulfur  dioxide  is  passed  through  to 
saturation  and  the  phenyl  chloro-arsine  acetic  acid  separates  in  the  form  of  plates. 
The  yield  is  practically  quantitative.  The  product  is  purified  by  crystallization  from 
chloroform  and  then  melts  at  102-3°.  Phosphorus  pentachloride  in  chloroform  solu- 
tion converts  the  substance  into  phenyl  dichloro-arsine. 

Analyses.  Subs.,  0.2000:  required  15.8  cc.  of  0.09205  N  I.  Calc.  for  C8H8O2ClAs: 
As,  30.4.  Found:  30.7. 

Subs.,  0.5000:  AgNO3,  0.3430.     Calc  for  C8H8O2ClAs:  Cl,  14.4.     Found:   14.3. 

Phenyl  Bromo-arsine  Acetic  Acid,  C6H,>AsBrCH2CO2H.— This  is  produced  in  a 
manner  analogous  to  that  for  the  chloro  compound  and  after  recrystallization  from 
chloroform  melts  at  113-4°. 

Analysis.  Subs.,  0.5000:  AgNO3,  0.2880.  Calc.  for  C8H8O,BrAs:  Br,  27.5. 
Found:  27.1. 

Phenylarsino  Acetanilide,  C6H6As(O2H)CH2CONHC6H6.— A  solution  of  35  g- 
of  phenyl  dichloro-arsine  in  65  cc.  of  10  N  sodium  hydroxide  solution  is  made  and  with 
mechanical  stirring  28  g.  of  chloro-acetanilide21  is  added.  After  3  hours,  when  the  re- 
action is  complete,  the  solution  is  diluted  with  an  equal  volume  of  water  before  proceed- 
ing in  the  usual  way.  The  product  weighs  50  g.  after  wastiing  with  water  and  drying. 
It  is  purified  by  crystallization  from  water  and  then  forms  small  needles  melting  at 
182-3°  with  evolution  of  gas. 

Analysis.  Subs.,  0.2000 :  required  12.2  cc.  of  0.09205  N  I.  Calc.  for  Ci4HuO3NAs : 
As,  23.5.  Found:  23.7. 

21  THIS  JOURNAL,  39,  1439  (1917). 


814  A.  J.  QUICK  WITH  ROGER  ADAMS 

Phenyl  Bromo-arsine  Acetanilide,  CeHsAsBrCHaCONHCeHc. — This  product  is 
•  made  in  a  manner  similar  to  that  for  phenyl  bromo-arsine  acetic  acid,  using  20  g.  of 
phenylarsino  acetanilide,  10  cc.  of  glacial  acetic  acid,  20  cc.  of  constant-boiling 
hydrobromic  acid  and  30  cc.  of  water  containing  a  few  crystals  of  potassium  iodide. 
After  saturation  with  sulfur  dioxide,  an  oil  separates  which  solidifies  on  standing. 
The  compound  is  crystallized  from  methyl  alcohol,  and  then  melts  at  108-110°. 

Analysis.  Subs.,  0.4000:  AgNOa,  0.1900.  Calc.  for  Ci4Hi8ONBrAs :  Br,  21.9. 
Found:  22.4. 

Phenylarsino  Acetphenetidine,  C6H6As  (O2H)  CH2CONHCcH4OC2H6(£) .  —  The 
reaction  between  18  g.  of  chloro-acetphenetidine22  and  19  g.  of  phenyl  dichloro- 
arsine  in  35  cc.  of  10  N  sodium  hydroxide  solution  takes  place  and  is  complete  in  a  few 
hours.  The  product  crystallizes  from  alcohol  in  needles  which  melt  at  175°  with  de- 
composition. 

Analyses.  Subs.,  0.2000,  0.2000:  required  10.70,  10.75  cc.  of  0.1038  N  I.  Calc. 
for  Ci6H1804NAs:  As,  20.6.  Found:  20.8,20.9. 

Phenylarsino  Aceto-arsanilic  Acid,  CeHeAs^^C^CONHCeHiAsOsH^).— 
A  solution  of  31  g.  of  sodium  chloro-acetoarsanilate23  in  50  cc.  of  water  is  added  gradually 
to  22  g.  of  phenyl  dichloro-arsine  in  45  cc.  of  10  N  sodium  hydroxide  solution.  The 
reaction  is  complete  in  2  hours.  The  chalky  white  material  is  extracted  with  a  large 
amount  of  hot  water,  then  with  hot  alcohol,  and  finally  dried  at  110°.  As  ix  is  insoluble 
in  water  or  the  common  organic  solvents,  it  cannot  be  recrystallized.  It  may  be  dis- 
solved in  alkali,  however,  and  reprecipitated  by  acidification.  It  does  not  melt  below 
250°. 

Analyses.  Subs.,  0.2000,  0.2000:  required  17.4,  17.4  cc.  of  0.1038  N  I.  Calc.  for 
Ci4H15O6NAs2:  As,  33.8.  Found:  33.8,  33.8. 

Phenylarsino  0-Aceto-amino  Benzoic  Acid,  C6H6As(O2H)CH2CONHC6H4- 
COzH-(o).—  A  solution  of  22.5  g.  of  sodium  0-chloro-aceto-amino  benzoate24  in  50  cc.  of 
water  is  added  to  22  g.  of  phenyl  dichloro-arsine  in  40  cc.  of  10  N  sodium  hydroxide 
solution.  The  reaction  takes  only  a  short  time  for  completion.  (The  sodium  o-chloro- 
aceto-amino  benzoate  is  prepared  in  a  similar  manner  to  the  preparation  of  p-chloro- 
aceto-amino  benzoic  acid  described  below.)  The  product  is  purified  by  boiling  the 
alkaline  solution  with  animal  charcoal,  filtering  and  reprecipitating  with  hydrochloric 
acid.  It  melts  at  198-200°  with  decomposition. 

Analysis.  Subs.,  0.2000 :  required  11.9  cc.  of  0.09205  N  I.  Calc.  for  CnHuO|NAs : 
As,  20.6.  Found:  20.4. 

/3-Phenoxy-ethyl  Phenyl-arsinic  Acid,  C6H<^s(O2H)CH2CH2OC6H5.— The  reaction 
between  45  g.  of  /3-phenoxy-ethyl  bromide,  45  g.  of  phenyl  dichloro-arsine  and  80  cc.  of 

10  N  sodium  hydroxide  solution  requires  4  to  6  hours  for  completion.     Heating  and 
mechanical  stirring  are  necessary  to  get  good  results.     The  small  excess  of  unchanged 
halide  is  removed  first  before  isolating  the  product.     The  substance  separates  as  an 

011  which  soon  crystallizes.     After  recrystallization  from  water  it  melts  at  122-3°  and 
weighs  about  20  g. 

Analysis.  Subs.,  0.2000:  required  14.3  cc.  of  0.09205  AT  I.  Calc.  for  CuHisOsAs: 
As,  24.5.  Found:  24.6.  • 

Ethylene  Diphenyl-diarsinic  Acid,  C2H4(C6H6AsO2H)2. — The  reaction  between  32  g. 
of  phenyl  dichloro-arsine,  120  cc.  of  10  N  sodium  hydroxide  solution  and  60  g.  of  ethyl- 

22  THIS  JOURNAL,  41, 1453  (1919). 
28  Ibid.,  41, 1810(1919). 
2<  Ber.,  38,  1684  (1905). 


AUPHATIC  ARSONIC  AND  ARSINIC  ACIDS  815 

ene  bromide  requires  4  to  8  hours  for  completion.  Heating  and  mechanical  stirring  are 
necessary.  The  product  separates  as  an  oil.  On  dissolving  in  dil.  ammonium  hydroxide, 
filtering  and  again  precipitating  by  careful  acidification  with  hydrochloric  acid,  an  oil  is 
formed  which  gradually  solidifies.  The  product  may  be  recrystallized  from  hot  water  or 
alcohol  and  melts  at  209-11°. 

Analysis.  Subs.,  0.2000:  required  21.7  cc.  of  0.09205  N  I.  Calc.  for  CuHieO^s-j: 
As,  37.7.  Found:  37.3. 

Subs.,  0.2000:  required  8.8  cc.  of  0.135  N  NaOH.     Found:  8.4  cc. 

/>-Amino-phenyl  Dichloro-arsine  Hydrochloride,2*  (/OC^sCeHtNHiHCl. — This 
product  is  precipitated  in  practically  quantitative  yields  when  a  stream  of  sulfur  dioxide 
is  passed  into  a  solution  of  one  part  of  arsanilic  acid  dissolved  in  3  parts  of  cone,  hydro- 
chloric acid.  A  crystal  or  two  of  potassium  iodide  is  added  as  a  catalyst. 

£-Amino-phenylarsino  Acetanilide,  (£)H2NC6H4As(O2H)CH2CONHC6H5.— This 
substance  is  prepared  in  the  usual  way  from  58  g.  of  £-amino-phenyl  dichloro- 
arsine  hydrochloride  in  100  cc.  of  10  N  sodium  hydroxide  solution  and  34  g.  of  chloro- 
acetanilide.  The  reaction  is  complete  in  about  an  hour  but  is  allowed  to  stand  for 
several  hours.  The  product  may  be  purified  by  crystallizing  from  either  water  or  alcohol. 
It  melts  at  181-2°  with  decomposition. 

Analysis.  Subs.,  0.2000:  required  13  cc.  of  0.09205  N  I.  Calc.  for  CuHi5O3N2As : 
As,  22.4.  Found:  22.4. 

£-Aceto-amino-phenylarsino  Acetanilide,  (£)CH3CONHC6H4As(O2H)CH2CON- 
HC6H6. — This  compound  is  made  from  the  one  just  described  by  warming  for  15 
minutes  after  the  initial  reaction  has  taken  place,  with  a  slight  excess  of  acetic  anhydride. 
The  compound  which  separates  upon  diluting  with  water  is  washed  with  dil.  hydro 
chloric  acid,  then  with  water,  and  finally  dried.  It  crystallizes  from  hot  water  in 
plates  which  melt  at  205-6°  with  decomposition. 

Analyses.  Subs.,  0.2000,  0.2000:  required  11.65,  11.65  cc.  of  0.09205  N  I.  Calc. 
for  Ci6H17O4N2As:  As,  19.9.  Found:  20.0,20.0. 

/>-Glycyl-aminophenylarsino  Acetanilide,  HO2CCH2NHC6H4As(O2H)CH2- 
CONHCells. — This  compound  is  prepared  from  />-amino-phenylarsino  acetanilide 
by  heating  10  g.  in  30  cc.  of  4%  sodium  hydroxide  solution,  with  7  g.  of  chloro- 
acetic  acid.  After  refluxing  for  3  to  4  hours  and  allowing  to  cool,  an  oil  separates  which 
solidifies  on  standing,  or  sometimes  a  solid  separates  directly.  The  compound  after 
crystallization  from  methyl  alcohol  melts  at  199°  with  decomposition. 

Analyses.  Subs.,  0.2000,  0.2000:  required  11.15,  11.2  cc.  of  0.09205  N  I.  Calc. 
for  Ci8Hi8O6N2As:  As,  19.1.  Found:  19.2,19.2. 

^-Amino-phenylarsino  Acetphenetidine,  (£)H2NC6H4.\s(O2H)CH8CONHC6H4O- 
C2H6(£). — The  reaction  between  21  g.  of  chloro-acetphenetidine  and  29  g.  of  p- 
amino-phenyl  dichloro-arsine  hydrochloride  in  50  cc.  of  10  N  sodium  hydroxide  solution 
is  complete  in  3  hours.  The  product  is  crystallized  from  alcohol,  then  melts  at 
211.5-212.5°. 

Analyses.  Subs.,  0.2000,  0.2000:  required  11.5,  11.5  cc.  of  0.09205  N  I.  Calc.  for 
CieHi9O4N2As:  As,  19.8.  Found:  19.8, 19.8. 

£-Aceto-ammo-phenylarsino  Acetphenetidine,  (£)CH3CONHC6H4(AsO2H)- 
CH2CONHC6H4OC2H6 (/>).—  The  product  is  made  from  the  one  just  described  by  using 
the  directions  given  under  £-aceto-amino-phenylarsino  acetanilide.  On  crys- 
tallization from  alcohol  it  melts  at  214-215*  with  decomposition. 

Analyses.  Subs.,  0.2000,  0.2000:  required  10.3,  10.3  cc.  of  0.09205  N  I.  Calc.  for 
Ci8H2iO6N2As:  As,  17.8.  Found-  17.7,  17.7. 

25  Ber.,  43,  917  (1910). 


816  A.  J.  QUICK  WITH  ROGER  ADAMS 

p-  Amino-phenylarsino  Acetoarsanilic  Acid,  (p)H2NC6H4As(O2H)CH2CONHC6- 
H4AsO3H2(£). — The  reaction  between  29  g.  of  chloro-aceto-arsanilic  acid  in  20 
cc.  of  10  Af  sodium  hydroxide  solution  and  sodium  £-amino-phenyl  arsenite  made  by  dis- 
solving 29  g.  of  £-amino-phenyl  dichloro-arsine  hydrochloride  in  50  cc.  of  10  N  sodium 
hydroxide  solution,  is  complete  within  3  hours.  The  product  is  purified  by  crystalliza- 
tion from  hot  water.  It  does  not  melt  below  350  °. 

Analyses.  Subs.,  0.2000,  0.2000:  required  18.8,  18.9  cc.  of  0.09205  N  I.  Calc.  for 
CuH1606N2As2:  As,  32.7.  Found:  32.3,32.5. 

/>-Aceto-amino-phenylarsino  Aceto-arsanilic  Acid,  (£)CH3CONHC6H4- 
As(O2H)CH2CONHC6H4AsOsH2 (/>).— This  compound  is  made  by  the  general  procedure 
already  described  under  the  other  aceto  compounds.  It  forms  in  poor  yields.  It  is 
purified  by  crystallization  from  hot  water.  It  does  not  melt  below  250°. 

Analyses.  Subs.,  0.2000,  0.2000:  required  17.3,  17.3  cc.  of  0.09205  N  I.  Calc.  for 
Ci6H18027N2As2:  As,  30.0.  Found:  29.7,29.9. 

£-Chloro-aceto-amino  Benzoic  Acid,  (p)ClCH2CONHC6H4CO2H.— A  suspension  of 
10  g.  of  p-amino  benzoic  acid  in  a  mixture  of  50  cc.  of  glacial  acetic  acid  and  50  cc.  of 
saturated  sodium  acetate  solution  is  treated  slowly,  with  vigorous  stirring,  with  chloro- 
acetyl  chloride.  A  white  amorphous  solid  precipitates,  is  filtered,  washed  and  dried. 
For  subsequent  work  the  crude  material  is  satisfactory,  but  it  may  be  purified  by  crys- 
tallization from  alcohol  and  then  has  a  melting  point  of  239  °. 

Analysis.  Subs.,  0.2000:  AgNO3,  0.1575.  Calc.  for  C8H8O3NC1:  Cl,  16.61. 
Found:  16.5. 

^-Amino-phenylarsino  £-Aceto-amino  Benzoic  Acid,  (/>)H2NC6H4As(O2H)- 
CH2CONHCsH4CO2H (/>).— This  reaction  between  42  g.  of  £-chloro-aceto-amino 
benzoic  acid  in  10  cc.  of  10  N  sodium  hydroxide  solution  and  58  g.  of  />-amino-phenyl 
dichloro-arsine  hydrochloride  in  100  cc.  of  10  N  sodium  hydroxide  solution  is  complete 
in  a  few  hours.  It  forms  needles  from  hot  water,  melting  at  217  °  with  decomposition. 

A nalysis.  Subs.,  0.2000 :  required  1 1 .4  cc.  of  0.09205  .V I .  Calc.  for  Ci4H]6OfiN2As : 
As,  19.8.  Found:  19.6. 

Summary 

1.  It  has  been  shown  that  aliphatic  arsonic  acids,  aliphatic  arsinic  acids 
and  aliphatic-aromatic  arsinic  acids  may  be  very  readily  prepared  by  the 
action  of  various  halogen  compounds  upon  an  aqueous  solution  of  sodium 
arsenite,  sodium  alkyl  arsenite  or  sodium  aryl  arsenite. 

2.  This  method  has  been  applied  to  the  preparation  of  several  alkyl 
arsonic  acids,  as  well  as  to  allyl  and  benzyl  arsonic  acids;  also  to  simple  and 
mixed  alkyl  arsinic  acids. 

3.  This  method  has  also  been  applied  to  the  preparation  of  many  com- 
pounds of  the  general  formula  RAs(O2H)CH2CONHR'  where  R  is  a  phenyl, 
^-amino-phenyl  or  ^-aceto-amino-phenyl  group  and  R'  is  a  phenyl  or 
substituted  phenyl  group.    The  compounds  dissolve  readily  in  aqueous 
alkalies,  giving  solutions  which  possess  relatively  low  toxicity  but  at  the 
same  time  only  a  slight  trypanocidal  action. 

URBANA,  ILLINOIS 


VITA 

The  writer  was  born  at  Theresa,  Wisconsin,  July  18,  1894. 
He  completed  his  elementary  school  course  in  that  village, 
and  was  graduated  from  the  Madison  (Wisconsin)  High 
School  in  1914  .  In  the  fall  of  the  same  year  he  entered  the 
University  of  Wisconsin  from  which  institution  he  received 
the  degree  of  Bachelor  of  Science,  June  1918,  and  the  degree 
of  Master  of  Science,  June  1919.  After  teaching  at  Vanderbilt 
University  for  one  year,  he  entered  the  University  of  Illinois 
in  the  summer  of  1920,  holding  a  fellowship  for  the  year 
1920-21. 

Appointments :  Assistant,  University  of  Wisconsin  1918-19 ; 
Instructor,  Vanderbilt  University  1919-20;  Fellow,  University 
of  Illinois  1920-21. 

Publications:  The  Preparation  of  p-Phenylenediamine 
and  Aniline  from  Their  Corresponding  Chlorobenzenes.  J.  Am. 
Chem.  Soc.  42,  1033,  (1920). 

The  Properties  of  Subsidiary  Valence  Groups.  I.  The  Mo- 
lecular Volume  relationships  of  the  Hydrates  and  Ammines 
of  Some  Cobalt  Compounds.  II.  Subsidiary  Group  Mobility  as 
Studied  by  the  Heat  Decomposition  of  Some  Cobaltammines. 
With  George  L.  Clark  and  William  D.  Harkins  J.  Am.  Chem. 
Soc.  42,  2483,  (1920). 


478642 

QS 

A*? 


JNIVERStTY  OF  CALIFORNIA 


